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Therapeutic effect of an altered peptide ligand derived from heat-shock protein 60 by suppressing of inflammatory cytokines secretion in two animal models of rheumatoid arthritis.
Lorenzo, N; Barberá, A; Domínguez, M C; Torres, A M; Hernandez, M V; Hernandez, I; Gil, R; Ancizar, J; Garay, H; Reyes, O; Altruda, F; Silengo, L; Padrón, G.
Affiliation
  • Lorenzo N; Biomedical Research Department, Center for Genetic Engineering and Biotechnology, Havana, Cuba. noraylis.lorenzo@cigb.edu.cu
Autoimmunity ; 45(6): 449-59, 2012 Sep.
Article in En | MEDLINE | ID: mdl-22686732
Rheumatoid arthritis is a systemic autoimmune disease mediated by T cells. Productive engagement of T cell receptors by major histocompatibility complex-peptide leads to proliferation, differentiation and the definition of effector functions. Altered peptide ligands (APL) generated by amino acid substitutions in the antigenic peptide have diverse effects on T cell response. We predicted a novel T cell epitope from human heat-shock protein 60, an autoantigen involved in the pathogenesis of rheumatoid arthritis. Three APLs were designed from this epitope and it was demonstrated that these peptides induce the activation of T cells through their ability to modify cell cycle phase's distribution of CD4+T cells from RA patients. Also, IL-17, TNF-α and IL-10 levels were determined in PBMC from these patients. Unlike the wild-type peptide and the other two APLs, APL2 increased the IL-10 level and suppressed IL-17 secretion in these assays. Therapeutic effect of this APL in adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models was also evaluated. Clinical score, histopathology, inflammatory and regulatory cytokine concentration were monitored in the animals. APL2 efficiently inhibited the progression of AA and CIA with a significant reduction of the clinical and histopathologic score. Therapeutic effect of APL2 on CIA was similar to that obtained with MTX; the standard treatment for RA. This effect was associated with a decrease of TNF-α and IL-17 levels. These results suggest that the therapeutic effect of APL2 is mediated in part by down-regulation of inflammatory cytokines and support the potential use of APL2 as a therapeutic drug in RA patients.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / Arthritis, Rheumatoid / Cytokines / Chaperonin 60 / Disease Models, Animal Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Autoimmunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2012 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peptides / Arthritis, Rheumatoid / Cytokines / Chaperonin 60 / Disease Models, Animal Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Autoimmunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2012 Document type: Article Affiliation country: Country of publication: